Real World Use of the Pediatric Disease Risk Index for Allogeneic Hematopoietic Cell Transplantation in Patients with Acute Lymphoblastic Leukemia and Acute Myeloid Leukemia: A Multicenter Study

Introduction To determine the risk of relapse of hematologic malignancies after allogeneic hematopoietic cell transplantation (allo-HCT), a disease risk index (DRI) tool has been used extensively for adult patients. In 2021 a validated DRI, considering age and disease status, for pediatric patients was developed by Qayed et al. (Blood, 2021, 137[7]). Objectives We assessed this pediatric DRI in a tri-institutional dataset of pediatric patients who underwent allo-HCT for acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML). Methods We retrospectively analyzed data from patients ≤18 years old receiving their first allo-HCT for ALL or AML between 2008-2019 at three large academic medical centers. Patients were grouped into low, intermediate, and high risk (for ALL) or low/intermediate, high, and very high risk (for AML), based on this new, pediatric DRI tool. Main outcomes of interest were leukemia-free survival (LFS) and relapse. Other outcome of interest was non-relapse related mortality (NRM). Fine and Gray competing risk models and Cox proportional hazard models were used for statistical analyses. Results 348 ALL patients were included; median age at HCT was 9 years (range 0.5 – 18). Based on the pediatric DRI tool, 136 (39.1%) patients were low, 176 (50.6%) were intermediate and 36 (10.3%) were high risk. Cumulative incidence of relapse for the low, intermediate, and high-risk groups were 14.4% (index), 29.6% (hazard ratio [HR] 2.1, 95% confidence interval [CI] 1.3-3.4, p=0.0036) and 39.3% (HR 3.2, 95% CI 1.6-6.4, p=0.0011) respectively (figure 1a). LFS at 5 years was 73% (index), 49.6% (HR 2, 95%CI 1.4-2.9, p=0.0003) and 22.2% (HR 5.1, 95%CI 3.1-8.4, p<0.001), respectively (figure 1b). Cumulative incidence of NRM was 9.8% (index), 16.7% (HR 1.5, 95%CI 0.9-2.7, p=0.15) and 34.1% (HR 3.5, 95%CI 1.7-7.2, p=0.0006), respectively.316 AML patients were included; median age 9.2 years (range 0.5 – 18 at HCT); 131 (41.5%) patients were low/intermediate, 110 (34.8%) were high and 75 (23.7%) were very high risk. Cumulative incidence of relapse for the low/intermediate, high, and very high-risk groups were 19.5% (index), 29.9% (HR 1.5, 95%CI 0.9-2.5, p=0.1) and 49.8% (HR 3.1, 95% CI 1.9-5.1, p<0.001) respectively (figure 1c). LFS at 5 years was 60% (index), 50.2% (HR 1.3, 95%CI 0.9-1.9, p=0.174) and 24.5% (HR 3, 95%CI 2.1-4.4, p<0.001), respectively (figure 1d). Cumulative incidence of NRM was 15.5% (index), 14.1% (HR 1, 95%CI 0.5-1.8, p=0.91) and 20.2% (HR 1.5, 95%CI 0.8-2.8, p=0.19), respectively. Conclusion In this multicenter real-world pediatric ALL and AML cohort, we confirm that using the pediatric DRI tool can predict risk of relapse and leukemia-free survival effectively, especially in the higher risk groups. These analyses further validate this tool, to guide standardized risk stratification in pediatric HCT for clinical decision-making and research purposes.